PROJECT SUMMARY: OVERALL The University of Kansas Alzheimer's Disease Center (KU ADC) promotes research into Alzheimer's disease (AD), brain disorders relevant to AD, and brain aging. We provide support, services, datasets, and biospecimens to institutional, regional, national, and international investigators. The KU ADC transforms AD-relevant research at our home institution and is an indispensable part of the KU neuroscience landscape. We benefit from and enhance an institutional T32 program, receive regular support from an institutional neuroscientist training fund, work closely with KU departments on neuroscientist faculty recruitment, and are a key component of the KU Institute for Neurologic Discoveries (KU IND). We further maintain interactive collaborations with other KU entities including the KU Landon Center on Aging (LCOA), Clinical Translational Science Award (CTSA) Center, NeuroNext site, and KU Cancer Center. We create AD-related clinical and educational infrastructure, making us a vital community and regional set-piece. While the KU ADC promotes an array of AD research, a prominent Center objective is to support, promote, and advance studies that address the causes and consequences of altered energy metabolism in aging and AD. Changes in energy metabolism (i.e, bioenergetics) have been linked to brain aging and AD. The KU ADC has developed a unique infrastructure that enables innovative research pertinent to basic, translational, and clinical energy metabolism-relevant questions. We are uniquely positioned to explore how altered energy metabolism contributes to brain aging and AD, and test the therapeutic potential of energy metabolism manipulations for the treatment of AD. We currently support state of the art programs that are testing the effects of physical exercise and dietary interventions on brain health, developing pharmacologic approaches to manipulate brain energy metabolism, exploring the contribution of mitochondrial genes to AD, and validating mitochondrial and other energy metabolism-related biomarkers. By advancing our understanding of energy metabolism's role in AD at multiple levels, developing novel capabilities, and testing innovative approaches intended to measure, characterize, and treat AD energy metabolism dysfunction we address a critical AD knowledge gap and position ourselves to potentially shift current AD research and clinical practice paradigms. Our first funding cycle (2011-16) focused on Center infrastructure, and our second funding cycle will extend our portfolio of federally funded investigator projects to further complement the first class, innovative research programs we currently support. Through these efforts and the research infrastructure we provide, we will pursue our mission to develop interventions that can prevent and treat AD. We will accomplish these goals through the following Specific Aims: (1) Advance AD and brain aging research; (2) Serve as a Midwestern hub for AD research, clinical care, and education; and (3) Enhance the ADC network.